**3. Plaque morphology**

The atherosclerotic process in the carotid arteries begins with a thickening of the intima-media complex and, according to factors of disease progression can reach arterial occlusion, through‐ out intermediate stages of mild, moderate and severe stenosis. Moreover, depending on several factors, the structure of the plaque can show different evolutionary behaviors, from simple stable plaque, fibrotic, and non stenotic, to that hemorrhagic, ulcerated, with rupture that produces severe stenosis and strokes. Carotid risk factors are identical to those mentioned for coronary disease.[79,80]

#### **3.1. Correlation between plaque morphology and cerebral symptoms**

The incidence of cerebrovascular events depends primarily on the degree of carotid stenosis but plaque structure is also relevant, as well as the speed of progression of plaque, and consequent carotid disease stenosis and also the presence of systemic thrombogenic factors. [81-83]

Several studies have described a good correlation between intraplaque hemorrhage (IPH) with ulceration and cerebrovascular symptoms.[25,53] According to Bluth the plaque structure is even more important than the degree of stenosis, in predicting neurologic events. [84]

Bearing in mind than more than 40 % of the patients with transient ischemic attacks later may suffer a stroke some authors believe that these stroke occur because plaques with IPH are unstable.[25,28,53] Embolization of fibrin and platelets and/or atherosclerotic material from the plaque itself will continue.

Other points to consider is the necessity of interventionally treating an asymptomatic carotid artery disease are: age 80 years or less, life expectancy higher tan 5 years, hemispheric hypoperfusion, significant intracerebral vascular disease,unstable carotid plaque, rapid progression of the stenoses, presence of silent cerebral infarcts, neck radiotherapy and the

As it can be seen, up to date criterium for percentage stenoses in this group of patients are

Finally and taking into consideration the mechanisms of atherosclerosis: cells component behavior, IPH, biology and gene expression, it can be seen in the literature a new tendency of treatment in animal models. However, attention should therefore focus on the processes of plaque breakdown andt hrombus formation in humans, whereas the use of animal models should probably be reserved for studying the function of particular genes and for investigating isolated features of plaques,such as the relationshipbetween cap thickness and plaque stability. [76] In this connection, Peter et al [77] described a ApoE(-/-) mice mouse model reflecting human atherosclerotic plaque instability in which atorvastatinwas used aimed at preventing plaque rupture. They concluded that distinctly expressed genes andmicroRNAscan be linked to plaque instability.On the other hand, Forte et al described the role of polyamines in reducing carotid arteriotomy-induced (re)stenosis s in vitro and in a rat model suggesting a novel

The atherosclerotic process in the carotid arteries begins with a thickening of the intima-media complex and, according to factors of disease progression can reach arterial occlusion, through‐ out intermediate stages of mild, moderate and severe stenosis. Moreover, depending on several factors, the structure of the plaque can show different evolutionary behaviors, from simple stable plaque, fibrotic, and non stenotic, to that hemorrhagic, ulcerated, with rupture that produces severe stenosis and strokes. Carotid risk factors are identical to those mentioned

The incidence of cerebrovascular events depends primarily on the degree of carotid stenosis but plaque structure is also relevant, as well as the speed of progression of plaque, and consequent carotid disease stenosis and also the presence of systemic thrombogenic factors.

Several studies have described a good correlation between intraplaque hemorrhage (IPH) with ulceration and cerebrovascular symptoms.[25,53] According to Bluth the plaque structure is even more important than the degree of stenosis, in predicting neurologic events. [84]

Bearing in mind than more than 40 % of the patients with transient ischemic attacks later may suffer a stroke some authors believe that these stroke occur because plaques with IPH are

necessity of a coronary by pass surgery. [66-74]

therapeutic approach for this pathophysiological process. [78]

**3.1. Correlation between plaque morphology and cerebral symptoms**

higher than in the ACAS study (60%). [75]

46 Carotid Artery Disease - From Bench to Bedside and Beyond

**3. Plaque morphology**

for coronary disease.[79,80]

[81-83]

As was mentioned, Geroulakos et al[81] classified ultrasonographic carotid plaques in 5 different types of stenosis, and correlated plaque type with symptomatology (not with pathology), showing the predominance of echolucent plaques in symptomatic patients with stenosis > 70 percent (see below) From the histologic point of view it was found that 50 % of the IPH had connections with the lumen while 20 % had not.[30] Lusby et al[25] showed that "haemorrhage in carotid atheromatous plaques plays a unique and major role in the develop‐ ment of cerebrovascular disease". IPH was not only identified in most symptomatic patients but also a close relationship was established between the onset of symptoms and the presence of plaque haemorrhage. Seeger et al[81-85] reported that the composition of plaques from symptomatic patients is significantly different from those asymptomatic. The former contains more total lipid and cholesterol, and less collagen and calcium.

Johnson et al [86] classified asymptomatic plaques according to ultrasonographic characteris‐ tics into calcified, dense and soft. At the end of a 3 year follow-up a large proportion of asymptomatic patients with soft plaques had become symptomatic, while a small proportion of those with calcified plaques have developed symptoms. Hennerici et al [87] reported that patients with fibrous carotid plaques had a tendency to remain stable while plaque progression was common in those with soft and complex calcified plaques. Spontaneous regression of minor carotid atheroma occurred in soft plaques corresponding to a reduction in plaque volume while fibrous and calcified plaques did not regress. [87]

Despite that currently the presence of symptoms and percentage of luminal narrowing remain the most useful predictors of transitory ischemic cerebral attacks or stroke risk, [3,75,88,89] there is a body of evidence that plaque morphology is crucial in the development of its natural history.

Regarding the relationship of IPH with a higher prevalence of symptoms or hemorrhagic stroke, the results are contradictory. [23-64] However, current guidelines recommend report‐ ing the plaque structure in question and that in occasions define therapeutic behaviors. [82-83]

There are several reasons that make knowledge of plaques structure very important. It is well known that fibrous plaques, are predominantly collagen in content, showing a highly echo‐ genic quality and being generally homogeneous in texture. When lipid content of the plaque increased, the plaque turns more echolucent. [84] Complex plaques protrude more frequently into the lumen presenting high incidence of surface irregularities and ulcers. [60] Several authors found that the incidence of IPH, histologically assessed, in symptomatic carotid stenosis is higher than 90 %. [25,44,53,99] Imparato et al, prospectively studied 376 carotid artery plaques concluding that IPH was strongly associated with the presence of cerebrovas‐ cular symptoms and it was the main characteristic of the carotid plaque that correlated statistically with the presence of symptoms. [44] O´Donnel theorized that IPH is the most common morphologic characteristic in symptomatic patients. [60]

### **3.2. B-mode ultrasound and pathology correlation**

In the 80´s, several authors attempted to describe plaque morphology and the presence of ulceration by ultrasonographic imaging. However, results were not convincing [90,91]. Other authors mentioned only relevant the percentage of carotid stenosis [92,93].

The accuracy of the carotid ultrasonography procedure in assessing the percentage of luminal diameter narrowing is well established [94,95].Percentage of stenosis has been the main point of interest for noninvasive carotid testing due to its correlation with stroke risk.[96,97]

Developed technics in ultrasound (US) permit a more detailed analysis and accurate informa‐ tion about the plaque morphology. This technique is useful to evaluate the natural history and the stroke risk associated to the lesions.

High-resolution B-mode ultrasonography (B-mode) seems advantageous over arteriography for characterizing atherosclerotic plaque. [53] The method can identify those lesions that place the patient at risk for transient ischemic attacks.

It was suggested that echolucent plaques have increased lipid and cholesterol levels, making them unstable and prone to rupture and hemorrhage. On the other hand, the echogenic plaques which contain significantly more fibrin and collagen are more stable and therefore less likely to cause complications. [81,85] There is a paper correlating these two ultrasonic types of plaques with whole frontal and/or transverse histological sections, correlating the B mode ultrasonographic diagnosis of at carotid arteries with their respective pathological examina‐ tions assessing US accuracy. [98]

According to Lehay, [99] Bluth, [84] Goes [100] and the recommendations from the Commit‐ tee on Standards in Non - invasive Vascular Testing, [101] carotid plaques were classified as homogeneous or heterogeneous.Butthese two groups arose from categorizing the plaques into 4 types according to the scale of l to 4 based on the Geroulakos' classification [81]. In this classification, Type 1 corresponded to uniformly sonolucent; type 2, predominantly sonolu‐ cent; type 3 predominantly echogenic and type 4 uniformly echogenic. In this way types l and 2 corresponded to heterogeneous plaques and types 3 and 4 to homogeneous plaques. (Figures 13 and 14)

The analysis of the complex plaque structure regards defining histological types [98]:


macroscopic hematoma within the arterial wall with or without extension through the

**Figure 14.** Panel A: it can be seen between arrows a carotid plaque containing predominantly echogenic areas (type 3 )that generally correspond to fibrous tissue which gives it stability Panel B.This carotid plaque (type 4) is practically

**Figure 13.** Panels A and B correspond to type 1 plaques-. The arrows indicate fully anechoic stenotic plaques which may correspond to fatty tissue and / or blood which indicate the instability of the same. Panel C Carotid plaque type 2 showing dense echoes (white color) alternating with most hypoechoic or anechoic areas(in black) which indicate pla‐

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**•** Hemorrhage is identified by disruption of red blood cells and macrophage engulfment of hemosiderin, to distinguish it from surgical related hemorrhage consisting in preserved

luminal surface.

composed by echogenic areas (between arrows).

que instability

erythrocytes.

**•** Inflammation was described as chronic inflammatory infiltrates (lymphocytes, histiocytes, macrophages and mast cells) within the plaque itself. Hemorrhage was identified by a Carotid Artery – Pathology, Plaque Structure – Relationship between Histological Assessment, Color Doppler... http://dx.doi.org/10.5772/57157 49

**3.2. B-mode ultrasound and pathology correlation**

48 Carotid Artery Disease - From Bench to Bedside and Beyond

the stroke risk associated to the lesions.

tions assessing US accuracy. [98]

13 and 14)

lesion"[26]

the patient at risk for transient ischemic attacks.

In the 80´s, several authors attempted to describe plaque morphology and the presence of ulceration by ultrasonographic imaging. However, results were not convincing [90,91]. Other

The accuracy of the carotid ultrasonography procedure in assessing the percentage of luminal diameter narrowing is well established [94,95].Percentage of stenosis has been the main point of interest for noninvasive carotid testing due to its correlation with stroke risk.[96,97]

Developed technics in ultrasound (US) permit a more detailed analysis and accurate informa‐ tion about the plaque morphology. This technique is useful to evaluate the natural history and

High-resolution B-mode ultrasonography (B-mode) seems advantageous over arteriography for characterizing atherosclerotic plaque. [53] The method can identify those lesions that place

It was suggested that echolucent plaques have increased lipid and cholesterol levels, making them unstable and prone to rupture and hemorrhage. On the other hand, the echogenic plaques which contain significantly more fibrin and collagen are more stable and therefore less likely to cause complications. [81,85] There is a paper correlating these two ultrasonic types of plaques with whole frontal and/or transverse histological sections, correlating the B mode ultrasonographic diagnosis of at carotid arteries with their respective pathological examina‐

According to Lehay, [99] Bluth, [84] Goes [100] and the recommendations from the Commit‐ tee on Standards in Non - invasive Vascular Testing, [101] carotid plaques were classified as homogeneous or heterogeneous.Butthese two groups arose from categorizing the plaques into 4 types according to the scale of l to 4 based on the Geroulakos' classification [81]. In this classification, Type 1 corresponded to uniformly sonolucent; type 2, predominantly sonolu‐ cent; type 3 predominantly echogenic and type 4 uniformly echogenic. In this way types l and 2 corresponded to heterogeneous plaques and types 3 and 4 to homogeneous plaques. (Figures

The analysis of the complex plaque structure regards defining histological types [98]:

erythrocytes sometimes accompanied by evidence of organization".

**•** Thrombus, described "a brightly eosinophilic mass of compacted fibrin and degenerating

**•** Ruptured plaque was defined as "disruption of the fibrous cap of a lesion that provoked exposure of the thrombogenic lipid core region to the flowing blood and was classified histologically as an irregular plaque surface with breaks in of loss of the fibrous cap often associated with surface thrombus directly overlying the lipid~rich necrotic core of the

**•** Inflammation was described as chronic inflammatory infiltrates (lymphocytes, histiocytes, macrophages and mast cells) within the plaque itself. Hemorrhage was identified by a

authors mentioned only relevant the percentage of carotid stenosis [92,93].

**Figure 13.** Panels A and B correspond to type 1 plaques-. The arrows indicate fully anechoic stenotic plaques which may correspond to fatty tissue and / or blood which indicate the instability of the same. Panel C Carotid plaque type 2 showing dense echoes (white color) alternating with most hypoechoic or anechoic areas(in black) which indicate pla‐ que instability

**Figure 14.** Panel A: it can be seen between arrows a carotid plaque containing predominantly echogenic areas (type 3 )that generally correspond to fibrous tissue which gives it stability Panel B.This carotid plaque (type 4) is practically composed by echogenic areas (between arrows).

macroscopic hematoma within the arterial wall with or without extension through the luminal surface.

**•** Hemorrhage is identified by disruption of red blood cells and macrophage engulfment of hemosiderin, to distinguish it from surgical related hemorrhage consisting in preserved erythrocytes.

Plaque morphology analyzed by US, identifying those unstable or complicated plaques found a very good correlation unless calcium deposits exist. [98]

In our research regarding interobserver agreement, there were 2 non-coincidences vs. 59

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51

Regarding the strictly classification in heterogeneous, homogeneous and calcified plaques, there were 59 coincidences, (96.7%) and 2 non-coincidences (3.3%), accuracy 98 %, K = 0.95

Coincidences not always were total. If we consider the fourth group in which operators agreed in plaques being heterogeneous but with difficulties in distinguishing IPH, calcium and lipids

When we considered agreement between observers and pathologist and taking into consid‐ eration the overall results from both observers, there was an agreement of 84% with the pathologist. When calcified plaques were not considered it is expected with 95% of confidence

When calcified plaques were considered, the percentage of coincidence fell to 67% (CI 0,95 54-79%). In others words calcified plaques clearly blurred the diagnosis of plaque structure. Operator l had an agreement of 67% with 18% of calcified plaques. Operator 2 had an agree‐

Regarding the coincidence of IPH between B - mode and pathology, operator 1 had an agreement of 50% (11/22) while operator 2 agreed in 65 % of the cases (11 / l7). The pathologist diagnosed IPH in 33 cases, therefore both observers, together were able to detect IPH in only

This investigation has correlated the ultrasound aspect of carotid atheromatous plaques with pathology demonstrating the highest incidence of intraplaque hemorrhage (IPH) in those

**Figure 16.** A.Two dimensional and color ultrasound image displays a very tight stenosis (between arrows) caused by an anechoic plaque (large arrow) B. The corresponding gross morphology shows an irregular stenotic plaque com‐ posed by a brownish tissue (arrow). C. Microscopically this plaque belongs to an intraplaque hemorrhage (arrow).

complex, irregular and heterogeneous producing stenosis 98. (Figure 16)

coincidences (efficacy 98%), K = 0.956, demonstrating very good agreement.

as non-coincidences, then the accuracy falls to 88.5 %.

ment of 79% with 8% of calcified plaques.

that US will agree with pathology in 70-93% of the cases (CI0,95).

(very good agreement).

l / 3 of the cases.

Mallory Trichrome

Ultrasonographically, calcium deposits are characterized by a highly echoreflective area with acoustical shadowing masking the real plaque structure below, resulting in a worse correlation between US and pathology.

Carotid plaques having calcium deposits correspond to a third classification (stable, unstable and calcium), as their evolution can be unpredictable. The presence of "acoustic shadows" that mask the true tissue structure is characteristic of this type of plaque on ultrasonography, making morphological interpretation difficult. [81] (Figure 15)

**Figure 15.** A type 5 calcified carotid plaque significantly reduces the lumen in the carotid bulb (between small arrows) The typically acoustic shadowing is clearly seen (big arrow)

In this sense, we published the results of an investigation showing ultrasonic vs pathologic correlation of carotid atheromatous plaques. This manuscript involved two ultrasonographers and one pathologist. [98] This work implied seventy-four carotid ultrasonographic studies randomly selected from a registry of 250 carotid endarterectomy specimens. (Thirteen of them had poor quality images and were excluded). The remaining 61 studies, belonging to 59 patients (2 bilateral endarterectomies) had been sent from five different laboratories and were analyzed blindly and independently by two different observers. There were 17 females and 42 males. Age ranged from 52 to 83 years (mean 68 years). A very good interobserver corre‐ lation was observed and, in turn, with histopathological findings. However, calcium plaques produced less agreement.

In our research regarding interobserver agreement, there were 2 non-coincidences vs. 59 coincidences (efficacy 98%), K = 0.956, demonstrating very good agreement.

Plaque morphology analyzed by US, identifying those unstable or complicated plaques found

Ultrasonographically, calcium deposits are characterized by a highly echoreflective area with acoustical shadowing masking the real plaque structure below, resulting in a worse correlation

Carotid plaques having calcium deposits correspond to a third classification (stable, unstable and calcium), as their evolution can be unpredictable. The presence of "acoustic shadows" that mask the true tissue structure is characteristic of this type of plaque on ultrasonography,

**Figure 15.** A type 5 calcified carotid plaque significantly reduces the lumen in the carotid bulb (between small arrows)

In this sense, we published the results of an investigation showing ultrasonic vs pathologic correlation of carotid atheromatous plaques. This manuscript involved two ultrasonographers and one pathologist. [98] This work implied seventy-four carotid ultrasonographic studies randomly selected from a registry of 250 carotid endarterectomy specimens. (Thirteen of them had poor quality images and were excluded). The remaining 61 studies, belonging to 59 patients (2 bilateral endarterectomies) had been sent from five different laboratories and were analyzed blindly and independently by two different observers. There were 17 females and 42 males. Age ranged from 52 to 83 years (mean 68 years). A very good interobserver corre‐ lation was observed and, in turn, with histopathological findings. However, calcium plaques

a very good correlation unless calcium deposits exist. [98]

50 Carotid Artery Disease - From Bench to Bedside and Beyond

making morphological interpretation difficult. [81] (Figure 15)

The typically acoustic shadowing is clearly seen (big arrow)

produced less agreement.

between US and pathology.

Regarding the strictly classification in heterogeneous, homogeneous and calcified plaques, there were 59 coincidences, (96.7%) and 2 non-coincidences (3.3%), accuracy 98 %, K = 0.95 (very good agreement).

Coincidences not always were total. If we consider the fourth group in which operators agreed in plaques being heterogeneous but with difficulties in distinguishing IPH, calcium and lipids as non-coincidences, then the accuracy falls to 88.5 %.

When we considered agreement between observers and pathologist and taking into consid‐ eration the overall results from both observers, there was an agreement of 84% with the pathologist. When calcified plaques were not considered it is expected with 95% of confidence that US will agree with pathology in 70-93% of the cases (CI0,95).

When calcified plaques were considered, the percentage of coincidence fell to 67% (CI 0,95 54-79%). In others words calcified plaques clearly blurred the diagnosis of plaque structure. Operator l had an agreement of 67% with 18% of calcified plaques. Operator 2 had an agree‐ ment of 79% with 8% of calcified plaques.

Regarding the coincidence of IPH between B - mode and pathology, operator 1 had an agreement of 50% (11/22) while operator 2 agreed in 65 % of the cases (11 / l7). The pathologist diagnosed IPH in 33 cases, therefore both observers, together were able to detect IPH in only l / 3 of the cases.

This investigation has correlated the ultrasound aspect of carotid atheromatous plaques with pathology demonstrating the highest incidence of intraplaque hemorrhage (IPH) in those complex, irregular and heterogeneous producing stenosis 98. (Figure 16)

**Figure 16.** A.Two dimensional and color ultrasound image displays a very tight stenosis (between arrows) caused by an anechoic plaque (large arrow) B. The corresponding gross morphology shows an irregular stenotic plaque com‐ posed by a brownish tissue (arrow). C. Microscopically this plaque belongs to an intraplaque hemorrhage (arrow). Mallory Trichrome

Correlation with histology shows that lipid rich regions are the least echogenic on US and calcified areas are the most. [81,98] Dense collagen is also very echogenic not associated with acoustic shadowing. For example O´Donnel [60] emphasized that plaque haemorrhage could be differentiated from lipid-laden plaque because the former was more irregular, echolucent, frequently associated with irregular borders, and randomly distributed through the plaque producing a non-homogeneous texture. The surface of the plaque with hemorrhage is usually irregular and ulcerated. Surface ulceration is unusual in lipid plaques. By contrast, plaque hemorrhage produces an echolucent area within the plaque, in which its degree may be correlated with the age of hemorrhage. [60]

**3.3. Magnetic resonance imaging – Patholgy correlation**

carotid intervention.

19 and 20).

**4. Carotid artery dolichoarteriopathies**

specific anatomical abnormalities called dolichoarteriopathies.

type 3, a prevalence of 5% to 25% has been described.[115,116]

tion of kinking and coiling to prevent stroke. [14,120,121]

disease, and aortic dissection. [112]

Although carotid ulltrasound is the method of choice to study the structure of carotid plaques MRI also plays a significant role. Singh et at, [109] in an interesting paper describing structural MRI findings in 98 asymptomatic carotid arteries with moderate stenosis (50-70%) and subsequent one year evolution to symptomatic status: 36 (36.7%) had IPH on NMR, with 6 cerebrovascular events, ie 16%, (2 stroke and 4 AIT) related to carotid IPH showed, compared to the absence of events in the carotid without IPH. Their statistical analyzes confirmed that the detection of IPH on NMR was associated with an increased risk of cerebrovascular events. In another relevant work involving MRI, Cheung et al [110] investigated the presence of IPH in the carotid arteries of 217 patients who had symptomatic stenosis less than 50%. IPH was

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53

detected in 13% related to the hemisphere ipsilateral symptoms and 7% contralateral.

In summary, we believe necessary to describe and report the B-mode characteristic of carotid plaques together with the percentage of luminal stenosis. Ultrasonic plaque description correlates with histogy. The adoption of plaque characterization despite of the degree of carotid stenosis would allow recognition of a high-risk subset of patients that may benefit from

Atherosclerosis is the most frequent cause of extracranial carotidartery disease. [111] However, although atheromatous pathology of the carotid bulb and bifurcation is a major causes of stroke, other causes of carotid disease may also cause vessel occlusion, such as fibrodysplasia, trauma (with subsequent dissection of carotid arteries), aortic arch pathology as in Takayasu

Among nonatheromatous alterations of the carotid arteries, interest has long been placed on

Carotid dolichoarteriopathies can be classified into three different types [113](Figure 17).Type 1: tortuosity – a nonrectilinear stretch of an artery with an angulation >90; type 2: loop – a 360 angulation of an artery on its transverse axis (''coil'' configuration) (Figure 18); type 3: kinking – the inflection of 2 or more segments of an artery with an internal angle of 90° or less. (Figures

Dolichoarteriopathies of carotid arteries are frequent, ranging between 10% and 45%. [114] For

Published studies have reached disparate conclusions with regard to the origin or cause of carotid dolichoarteriopathies, as well as their hemodynamic and prognostic significance. [114-119] Mukherjee and Inahara [119] proposed that carotid kinking would induce turbulent flow, thus favoring intimal ulceration, platelet deposition, and distal thrombus embolism. Other investigators similarly believe that a causal connection exists between cerebral flow alteration and severe carotid dolichoarteriopathies, to the point of proposing surgical correc‐

The anechoic or highly echolucent qualities of fresh hemorrhage are comparable with those of the lumen, being irregular and randomly distributed through the plaque (heterogeneous shape).

On the other hand, Bluth et al [84] found that the incidence of IPH in theheterogeneous type was 81 % vs. 3 % in the homogeneous plaques. Thus, the sensitivity and specificity of US to detect this lesion was 94 % and 88 % respectively.

Ultrasonography fails in detecting plaque ulceration even using color-flow Doppler assisted duplex, as was recently demonstrated by Sitzer et al. [102]

Hartmann et al [103] reported poor results between US and pathology concluding that visual assessment of B-mode images is not reliable. Lehay et al [99] found that plaques that caused a narrowing greater than 50% in the carotid lumen were more likely to be heterogeneous, suggesting that plaque appearance is a more relevant finding on preoperative duplex scanning than the percentage of carotid narrowing.

Taking all these concepts into consideration, decreased echogenicity would correspond either to lipid deposits or to hemorrhage within a plaque being both of them characteristic of instability. Lipid deposits appear more uniform and are less randomly distributed throughout the plaque.

Julian et al [104] divided plaques into two categories: "simple" composed of fibrous material and that do not generally cause stenosis greater than 50 %, and "complex" consisting of an atherosclerotic material, calcified deposits, surface fibrin, platelet material and hemorrhagic areas.

The European Carotid Plaque Study Group [105] correlated B-mode imaging studies with histology in 270 patients undergoing carotid endarterectomy. They concluded that US appearance of carotid plaque is related to histological composition being the echogenicity inversely related to the relative amount of soft tissue.

Backscattered radiofrequency derived signals devices have been applied for better character‐ ization of the different components of plaque structure[106-108].But this technique is more expensive and not always available in most laboratories so we consider that conventional good quality B-mode images allow a reliable differentiation between the three types of plaques.

### **3.3. Magnetic resonance imaging – Patholgy correlation**

Correlation with histology shows that lipid rich regions are the least echogenic on US and calcified areas are the most. [81,98] Dense collagen is also very echogenic not associated with acoustic shadowing. For example O´Donnel [60] emphasized that plaque haemorrhage could be differentiated from lipid-laden plaque because the former was more irregular, echolucent, frequently associated with irregular borders, and randomly distributed through the plaque producing a non-homogeneous texture. The surface of the plaque with hemorrhage is usually irregular and ulcerated. Surface ulceration is unusual in lipid plaques. By contrast, plaque hemorrhage produces an echolucent area within the plaque, in which its degree may be

The anechoic or highly echolucent qualities of fresh hemorrhage are comparable with those of the lumen, being irregular and randomly distributed through the plaque (heterogeneous

On the other hand, Bluth et al [84] found that the incidence of IPH in theheterogeneous type was 81 % vs. 3 % in the homogeneous plaques. Thus, the sensitivity and specificity of US to

Ultrasonography fails in detecting plaque ulceration even using color-flow Doppler assisted

Hartmann et al [103] reported poor results between US and pathology concluding that visual assessment of B-mode images is not reliable. Lehay et al [99] found that plaques that caused a narrowing greater than 50% in the carotid lumen were more likely to be heterogeneous, suggesting that plaque appearance is a more relevant finding on preoperative duplex scanning

Taking all these concepts into consideration, decreased echogenicity would correspond either to lipid deposits or to hemorrhage within a plaque being both of them characteristic of instability. Lipid deposits appear more uniform and are less randomly distributed throughout

Julian et al [104] divided plaques into two categories: "simple" composed of fibrous material and that do not generally cause stenosis greater than 50 %, and "complex" consisting of an atherosclerotic material, calcified deposits, surface fibrin, platelet material and hemorrhagic

The European Carotid Plaque Study Group [105] correlated B-mode imaging studies with histology in 270 patients undergoing carotid endarterectomy. They concluded that US appearance of carotid plaque is related to histological composition being the echogenicity

Backscattered radiofrequency derived signals devices have been applied for better character‐ ization of the different components of plaque structure[106-108].But this technique is more expensive and not always available in most laboratories so we consider that conventional good quality B-mode images allow a reliable differentiation between the three types of plaques.

correlated with the age of hemorrhage. [60]

52 Carotid Artery Disease - From Bench to Bedside and Beyond

detect this lesion was 94 % and 88 % respectively.

than the percentage of carotid narrowing.

inversely related to the relative amount of soft tissue.

duplex, as was recently demonstrated by Sitzer et al. [102]

shape).

the plaque.

areas.

Although carotid ulltrasound is the method of choice to study the structure of carotid plaques MRI also plays a significant role. Singh et at, [109] in an interesting paper describing structural MRI findings in 98 asymptomatic carotid arteries with moderate stenosis (50-70%) and subsequent one year evolution to symptomatic status: 36 (36.7%) had IPH on NMR, with 6 cerebrovascular events, ie 16%, (2 stroke and 4 AIT) related to carotid IPH showed, compared to the absence of events in the carotid without IPH. Their statistical analyzes confirmed that the detection of IPH on NMR was associated with an increased risk of cerebrovascular events. In another relevant work involving MRI, Cheung et al [110] investigated the presence of IPH in the carotid arteries of 217 patients who had symptomatic stenosis less than 50%. IPH was detected in 13% related to the hemisphere ipsilateral symptoms and 7% contralateral.

In summary, we believe necessary to describe and report the B-mode characteristic of carotid plaques together with the percentage of luminal stenosis. Ultrasonic plaque description correlates with histogy. The adoption of plaque characterization despite of the degree of carotid stenosis would allow recognition of a high-risk subset of patients that may benefit from carotid intervention.
